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Top 11 Scientific Health Benefits of Pregnenolone (including side effects)

Pregnenolone is a supplement that everyone should read about.  It has helped me by increasing mood, motivation, and brain function.  Pregnenolone feels like a steroid for the brain to me.

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Intro

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Pregnenolone and its sulfate (pregnenolone sulfate) are excitatory neurosteroids – they stimulate the brain (R).

Pregnenolone is the main steroid produced from cholesterol (R).

It is produced in three main organs: the brain, gonads and adrenal glands (R), but the salivary gland and white blood cells are also capable of producing pregnenolone (R, R).

Pregnenolone is neuroprotective and enhances learning and memory (R, R) and increases the amount of deep sleep (R).

Pregnenolone has a beneficial effect on mood (R, R).

Ever since the 1940s, pregnenolone was reported to have anti-stress and mood-elevating effects on factory workers, students, and pilots (R).

Pregnenolone has a beneficial effect in various neuropsychiatric disorders (R, R), and relieves anxiety and depression (R).

Pregnenolone is the main precursor of many other steroid hormones (R). For example, pregnenolone increases the level of other neurosteroids such as pregnenolone sulfate and allopregnanolone.

Allopregnanolone is another molecule that increases the growth of neurons, decreases cell death and inflammation (R).

Like most products that can’t be patented, pregnenolone doesn’t have large clinical trials for various conditions.  This is where Selfhacking comes in and testing out if pregnenolone works for you.

My Experience and What I Use

I’ve been taking pregnenolone for 3-4 years, on and off.  I really love it.  You need to find the right dosage.  Pregnenolone doesn’t work for a lot of my clients.  The most common issues with pregnenolone are that it gives people anxiety and they have more trouble sleeping.

For me, it will cause sleep issues if 1) I take too much and 2) I don’t exercise enough and 3) I don’t exercise enough earlier in the day.  Exercise makes pregnenolone convert to other hormones to produce cortisol.  If I exercise later in the day with pregnenolone, it makes me more wired than ordinarily (perhaps I have a larger cortisol spike).

I find when I was having chronic inflammation, I was deficient in pregnenolone.  I’m not deficient now, but since I have a very heavy workload, I use more up, so in these times it’s useful.

I am currently taking this pregnenolone.

Pregnenolone

  • Longevity9.5/10
  • Inflammation9.0/10
  • Mood9.6/10
  • Cognition9.5/10
  • Energy9.0/10

        Pros

  • Great for cognitive enhancement
  • Is relaxing and stimulating at the same time
  • Increases motivation
  • Increases wakefulness
  • Increase hormones
  • Good for libido
  • Good for longevity

        Cons

  • May increase anxiety for some
  • Can cause some sleep issues

The Good

1) Pregnenolone is a Nootropic and Boosts Cognitive Function

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Pregnenolone and pregnenolone sulfate act as signaling molecules in the brain where they stimulate neuronal activity (R, R).

Pregnenolone increases the growth of neurons (R).

Pregnenolone enhances myelination, enhances the formation of new synapses, and has neuroprotective properties.  Myelin is a fatty layer that electrically insulates nerves, and is essential for their proper functioning (R).

Pregnenolone sulfate enhances the survival of newborn neurons in adult mice (R).

Pregnenolone also improves neurological recovery (R).

Pregnenolone and pregnenolone sulfate protect neurons against cell toxicity and toxin-induced cell death (R, R).

Low blood levels of pregnenolone are found in the elderly, including those with dementia (R).

Nootropic Mechanism:

Pregnenolone regulates neuronal function by activating and deactivating GABAA, NMDA, sigma-1, cholinergic and dopamine receptors (R).

Pregnenolone sulfate decreases the activity of GABAA receptors, kainate, and AMPA receptors and increases the activity of NMDA receptors (R).  (This might be why pregnenolone increases anxiety in some.)

When bound to receptors, pregnenolone, and its metabolites cause a series of reactions, including the stabilization of microtubules, the increase of ion flux into cells, and dopamine release (R).

By regulating microtubules, pregnenolone may increase neuronal development and plasticity of neurons during aging (R).

Joe’s Experience: Pregnenolone boosts cognitive function for me and is one of my favorite nootropics.  It goes well with infrared therapy/LLLT.

2) Pregnenolone Improves Learning and Memory

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Pregnenolone/pregnenolone sulfate enhance learning and memory in mice and rats (R, R, R).

Pregnenolone/pregnenolone sulfate results in better performance of mice and rats in various mazes (R).

Pregnenolone sulfate blocks chemical-induced amnesia in rats (R, R).

Pregnenolone sulfate prevents learning and memory deficits induced by certain drugs (R).

Joe’s Experience: Pregnenolone boosts learning and memory for me.

3) Pregnenolone Stimulates Deep Sleep

Sleeping

Pregnenolone and its derivate allopregnanolone stimulate deep sleep in animal studies (R).

Low concentration of pregnenolone sulfate increased the amount of REM (paradoxical sleep), while high concentrations increased both REM and slow wave sleep (deep sleep) (R).

Pregnenolone increased the amount of time spent in deep sleep in human volunteers (R).

Deep sleep, in turn, helps consolidate memories.

Joe’s Experience: Pregnenolone is more likely to worsen your sleep than benefit it. I have found pregnenolone (at 50mg) delays sleep onset and results in less sleep for me.  Other people also report insomnia from these doses.

4) Pregnenolone Relieves Schizophrenia Symptoms

Pregnenolone can potentially be used to alleviate and treat certain symptoms of schizophrenia (R).

Pregnenolone levels are lowered in the brain of schizophrenic patients (R, R).

Elevations in pregnenolone and allopregnanolone after pregnenolone treatment in schizophrenia were correlated with cognitive improvements (R).

Treatment with pregnenolone sulfate reduced schizophrenia-like symptoms and rescued the cognitive deficits in mice (R).

Pregnenolone reduced symptoms in patients with schizophrenia and schizoaffective disorder (R).

Pregnenolone improved attention, verbal and working memory performance in schizophrenic patients (R, R).

Low dose pregnenolone together with antipsychotics reduced drug-induced side effects in schizophrenic patients (R).

5) Pregnenolone Boosts Mood and Relieves Depression

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Decreased pregnenolone and allopregnanolone levels have been linked to depression (R).

Pregnenolone has significant mood-stabilizing effect (R).

Pregnenolone enhances the activation of neurocircuits that control emotion (R).

Blocking allopregnanolone impairs social and emotional functioning (R).

In response to emotional cues, allopregnanolone reduces the activity in brain regions associated with the generation of negative emotion (R).

Pregnenolone reduces depression in patients with bipolar disorder, recurrent major depressive disorder and history of substance abuse/dependence (R, R).

A synthetic pregnenolone derivative acts as an antidepressant in rats (R).

Depressive disorders are associated with neuronal abnormalities in brain microtubule function (R).

By increasing formation and stability of tubules, pregnenolone increases neurite growth (R) – and can combat depression.

Joe’s Experience: Pregnenolone boosts mood and motivation quite a bit.  In fact, it increases mood and motivation more than anything else I’ve tried.

6) Pregnenolone is Anti-Anxiety

Patients with general anxiety disorder have significantly lower levels of pregnenolone sulfate (R).

Allopregnanolone (measured after taking pregnenolone) reduces self-reported anxiety (R).  

Pregnenolone reduces irritability in adults with autism spectrum disorder (R).

Allopregnanolone is a potent activator of GABA (A) (R).

Joe’s Experience: Pregnenolone does have anti-anxiety effects, but I’ve had some clients tell me it increases their anxiety.  For me, it makes me more emotional and more passionate.  This includes good and bad emotions.  For example, a breakup would feel worse if I’m taking pregnenolone, but you are more likely to fall in love, in my experience.

7) Pregnenolone Balances the Immune System

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Synthetic pregnenolone derivatives act as antiviral agents against Herpes Simplex Virus (R).

Pregnenolone suppresses immune cells to restore immune balance (homeostasis) (R).

8) Pregnenolone Increases Libido (Anecdotal)

I haven’t seen any studies with libido and pregnenolone, but I notice a difference and my clients often do.

This could be from increasing ‘downstream’ hormones such as progesterone, DHEA,testosterone, etc…

9) Pregnenolone Reduces Alcohol Preference and Intake

Acute but not chronic pregnenolone significantly reduces alcohol preference and intake in rats (R).

Pregnenolone treatment significantly reduces alcohol self-administration in rats (R).

10) Pregnenolone Kills Brain Cancer cells

Cancer

Pregnenolone induces glioma cell death (R).

11) Pregnenolone Protects from Cannabis Intoxication

Pregnenolone protects the brain from cannabis intoxication (R).

The administration of tetrahydrocannabinol (THC), the main active component of marijuana, substantially increases the production of pregnenolone (R).

Other

Pregnenolone has Anti-Arthritic, Anti-Ageing, and Anti-Fatigue properties.  It also lowers cholesterol (R).

See this chart.

The Bad

1) Pregnenolone Can Impair Memory

Pregnenolone sulfate impairs memory acquisition (R) and memory retention (R) in rats.

Allopregnanolone impaired learning in rats (R).

2) Pregnenolone Can Reduce Wakefulness

Pregnenolone sulfate promotes sleep and can impair wakefulness (R).

Safety of Pregnenolone

Studies conducted in the 1940s and 1950s showed that pregnenolone at 25–500 mg/day was safe and well tolerated in humans, with minimal side effects, and did not affect weight, heart rate, blood pressure, menstrual cycle, or glucose levels (R).

Pregnenolone Dosage

Pregnenolone is very safe as far as toxicity.

Generally, if you do get a side effect from pregnenolone, you can stop taking it and it will go away.  I’ve never heard of permanent negative effects.

I recommend starting out with 5mg if you’re healthy and make sure to pay attention to your sleep.

If you have schizophrenia or chronic inflammation, you will want to take 25mg a day (if your doctor thinks it’s a good idea).

What Else Increases Pregnenolone?

  • Lithium increases blood levels of allopregnanolone and pregnenolone in mice (R).

Other:

  • THC, the main active component of marijuana, substantially increases the production of pregnenolone (R)
  • Stress (R)
  • SSRIs and Antipsychotic drugs used for treating depression and bipolar disorder: clozapine, olanzapine and fluoxetine (Prozac) elevate pregnenolone levels in the brain and blood of rats (R).

Pregnenolone Goes Well With

Pregnenolone goes well with aromatase inhibitors so that it doesn’t convert to estradiol.

My favorite aromatase inhibitors include:

Inhibiting cortisol production may also help.

This way pregnenolone will go more to making progesterone, DHEA and testosterone instead of estradiol and cortisol.

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When to Taking Pregnenolone

I recommend taking it right upon awakening and exercising in the morning and an empty stomach – so that it gets absorbed quicker.

Pregnenolone on SelfDecode

Buying Pregnenolone

There are many dosages of pregnenolone you can buy.  You can either buy a smaller amount or larger amount and break up the capsule.

Comments

  1. Tim

    hi i was wondering, is there a specific form people take to notice a difference as i recall, orally its not very bioavailable if any at all.

    • Nattha Wannissorn

      Yes Joe uses one from Pure Encapsulations and Biomatrix (links in the article). The one from Biomatrix you can put the drops under your tongue or just rub it in through your skin. I put it under my tongue.

  2. Been taking it for 5 years. No cognitive improvements or bursts of energy to speak of. However, people guess my age range to be late thirties and I’m 60 this year, so maybe it is working.

  3. Gretchen Grieser

    Joe – I am a 51 year old female. I recently had my labs done. After reading your article I looked at my results. My Pregnenolone level is 9 ng/dL. My doctor gave me a bottle of 10 mg Pregnenolone tablets to take and said, “follow the instructions on the bottle”. The suggested use is 1 or more tablets a day as directed by your health care professional. I have been taken one tablet a day for a couple weeks but have not noticed any type of change. Any thoughts?

  4. peter aris

    increased my libido through increasing my testosterone and went as high as 50mg per day but had to lower as affected my sleep.now take 12 1/2mg 3 times per week,much better

  5. Isa

    Hi joe
    I have been taking pregnenolone for 24 years
    First recommended by a life extension employee
    I was 46 years old and having menopause symptoms . I started with 50mg and in the last five years I increased it to 100 mg
    I find that the 50 mg tablets by life extension are better for me then the 100mg. So I take 2 of the 50 mg
    Next week I will turn 70 years and I feel great
    I have tried to quit a few times to make sure it’s not psychological, and after 3 weeks I start noticing the lack of it.
    Old age starts creeping on me. I’m slower, more fatigued lacking energy
    I start again and I feel like 40 again
    This is my honest experience ! Not many people not even doctors know about pregnenolone!!
    I must note that the brain alertness is incredible
    I need it! I run two businesses and trade the stock market.
    Best of luck to all. It’s the first time I have the opportunity to share my experience with pregnenolone

    Isa

    • Maureen

      Wow! That’s really amazing! I just recently started supplementing with Pregnenolone and take 10 mg in the morning when I get up. Do you recommend I supplement it with Resveratrol?

  6. michelle frankie

    for me im still completely confused on this one..I for one have too high cortisol which u dont want and consequently when I take this supplement i feel really really bitchy like is that spiking cortisol ive been told i need adrenal support n all i knew were this and dhea…but actually im freagin luving this Relora ..and a tiny bit of dhea…I think I need to niix the preg even though it sounds good..i never feel anything good

  7. Hi Joe,

    Firstly good article I’m also a fan of Pregnenolone.

    As you mention “you need to find the right dosage.”
    I wonder what if any dosages you recommend.

    I currently have 30mg every other day. Is that about right as I have not been taking it for long so my levels are already probably too low. Once your levels are higher do you generally stick with 10mg?

    Thanks,

    Paul

  8. Santino

    I guess you are confusing something. The pregnenolone steal means that it is converted into progesterone to make cortisol. So there is not enough left to make DHEA.

  9. i cant believe it was not mentioned that pregnenolone is not bioactive orally. it has a lot of research showing this but yet it is completely absent in this article.

    • Joseph M. Cohen

      Reference? Something is causing similar benefits as is mentioned when ingested.

      What about sublingual?

  10. Dimoff

    Each time I take pregnenolone (And I’ve taken it hundreds of times) I can feel my liver afterwards. Similar to testosterone feeling.
    Plus, is my hair going to fall out from it in case I have the rest of the balding genes? Probably yes.

  11. Santino

    Hello Joseph,

    thanks for that article.

    I wonder why you think it is negative if pregnenolone get converted to cortisol. You know that cortisol is a very important hormone (you wrote yourself in another post).

    If your body takes the pregnenolone to make cortisol, he does it for a reason (for example because of a stress response). And I don’t see any negative point here.

    Actually, people often get sick because at some point, their adrenals are no longer able to give a strong enough cortisol response. Yes, high cortisol is associated with a lot of negative things (depression, impaired memory etc. etc.) However correlation is not causation and imagine you had the same stress but low cortisol levels. You more likely would get pretty sick (inflammatory diseases, fatigue, exhaustion).

    So I don’t feel there is a reason to worry that the body makes too much cortisol out of it. The body will make what he needs the most, and if that is cortisol, that other environmental factors should be changed (for example lowering stress).

    Also I don´t think that cortisol impairs immunity (only excess would do so). In fact if you have too low cortisol, your immunity is impaired. Dr. Jeffries had a lot of experience with patients and cortisol replacement and wrote the book “safe uses of cortisol”. His observation was that physiologic doses of cortisol increase the peoples ability to overcome infections.

    So why do you think that it bad if the body takes the extra pregnenolone to make cortisol?

    Another question I have for you, which would be cool to have a review about it progesterone.

    I think that progesterone can have many of the positive effects of pregnenolone and is an underestimated hormone in males. The body also can make cortisol if he needs it and the body also could make testosterone. It seems to help to balance the oestrogen/estradiol ratio and promotes an anti-inflammatory TH2-profile.
    It doesn’t have the possible negative side effects of pregnenolone (anxiety, irritability etc.). The only disadvantage for me would be that the body could not make DHEA (which could be supplemented as well, again without causing anxiety like pregnenolone does for many).

    What you think about hacking the system with progesterone in patients that have too low cortisol or have TH1 dominant inflammatory diseases?

    • Anthony

      100% agree with you on cortisol! I have seen the MOST profound improvements with my clients on physiologic use of hydrocortisone. Faster healing, better glucose metabolism and skyrocketing energy and sense of well being!

  12. I wonder if, in cases where memory appears to be negatively affected, if its potential GABA modulation is in play: I mean excessive neural inhibition could negatively impact on perception. On the other hand, a person who is for whatever reason, GABAergically dysfunctional, would likely become more capable of concentrating percepatory efforts, leading to results indiciative of improved memory. Or I might be parading my ignorance 😀

  13. Never been hot on the STEAL issue. Looks to me that once converted to DHEA, the preference is to STEAL (if I must use that word) from DHEA. Most men I see have tanked DHEA levels from a stress response the body cannot manage anymore. Very interesting topic and it dovetails into LOW T.

  14. Tania L

    What time of day should pregnenolone be taking and is it best taken with food or on an empty stomach?

    Interesting article. It seems odd that it appears to both help and impair memory. What’s up with that?

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